Serum Bactericidal Activity of Trovafloxacin Against Selected Anaerobic Pathogens

Stein, Gary E.; Citron, Diane M.; Tyrrell, Kerin L.; Goldstein, Ellie J. C.

doi:10.1006/anae.2001.0386

Cited by 3 publications

(3 citation statements)

References 18 publications

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“…They found that, although it was effective for the B. fragilis and E. coli combination, trovafloxacin was ineffective against the VREF, and, in that combination, it also had diminished killing activity of the B. fragilis. Stein et al [41] studied the serum bactericidal activity of trovafloxacin and found it to have prolonged cidal activity against B. fragilis, C. perfringens, and Peptostreptococcus magnus but not, after the first sampling period, against B. thetaiotaomicron. This diminished cidal activity is suggestive that speciation of B. fragilis group species may have therapeutic implications for patients receiving fluoroquinolone therapy.…”

Section: Trovafloxacinmentioning

confidence: 97%

Intra‐Abdominal Anaerobic Infections: Bacteriology and Therapeutic Potential of Newer Antimicrobial Carbapenem, Fluoroquinolone, and Desfluoroquinolone Therapeutic Agents

Goldstein¹

2002

CLIN INFECT DIS

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Intra-abdominal infections are biphasic, synergistic processes with early peritonitis and bacteremia due to aerobes and a later abscess component due to anaerobes. Although Bacteroides fragilis is the most commonly recognized pathogen, other anaerobes, including other members of the B. fragilis-group species, are major components of infection. Anaerobic bacteremia is often associated with an intra-abdominal source. New antimicrobial agents with anaerobic activity are in various stages of development for the therapy of intra-abdominal infections. The in vitro activity and the currently available sparse clinical data are reviewed for a new carbapenem (ertapenem), several fluoroquinolones (trovafloxacin, moxifloxacin, and gemifloxacin), and a desfluoroquinolone (BMS-284756).

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Section: Trovafloxacinmentioning

confidence: 97%

Intra‐Abdominal Anaerobic Infections: Bacteriology and Therapeutic Potential of Newer Antimicrobial Carbapenem, Fluoroquinolone, and Desfluoroquinolone Therapeutic Agents

Goldstein¹

2002

CLIN INFECT DIS

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“…Stein et al [85] have conducted several ex vivo studies of newer quinolones against anaerobic pathogens by measuring serum bactericidal titers over time. Following a single oral dose (200 mg) of trovafloxacin to healthy volunteers, prolonged (12-24-h) serum bactericidal activity was observed against isolates of B. fragilis (MIC, 0.125 mg/mL), C. perfringens (MIC, 0.094 mg/mL), and Peptostreptococcus magnus (MIC, 0.016 mg/mL).…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Fluoroquinolones and Anaerobes

Stein

Goldstein

2006

Clinical Infectious Diseases

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The usefulness of fluoroquinolones for the treatment of mixed aerobic and anaerobic infections has been investigated since these agents started being used in clinical practice. Newer compounds have increased in vitro activity against anaerobes, but clinically relevant susceptibility breakpoints for these bacteria have not been established. Pharmacodynamic analyses and corroboration by new data from clinical trials have enhanced our knowledge concerning the use of fluoroquinolones to treat selective anaerobic pathogens. These studies suggest that newer agents could be useful in the treatment of several types of mixed aerobic and anaerobic infections, including skin and soft-tissue, intra-abdominal, and respiratory infections. The major concerns with expanding the use of fluoroquinolones to treat anaerobic infections have been reports of increasing resistance in Bacteroides group isolates and the impact of these antibiotics on the incidence of Clostridium difficile-associated disease.

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“…This agent provides prolonged bactericidal activity in serum against common anaerobic pathogens and clinical efficacy for mixed aerobic-anaerobic infections (10,30). The methoxyfluoroquinolones gatifloxacin and moxifloxacin also have broad-spectrum activity against anaerobic organisms, especially respiratory pathogens (1,6,15).…”

Section: Discussionmentioning

confidence: 99%

Bactericidal Activities of Methoxyfluoroquinolones Gatifloxacin and Moxifloxacin against Aerobic and Anaerobic Respiratory Pathogens in Serum

Stein

Schooley

Tyrrell³

et al. 2003

Antimicrob Agents Chemother

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Gatifloxacin (Bristol-Myers Squibb) and moxifloxacin (Bayer) are new methoxyfluoroquinolones with broadspectrum activity against aerobic and anaerobic pathogens of the respiratory tract. In this investigation, we analyzed the bactericidal activity in serum over time of these antimicrobials against three aerobic (Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus) and four anaerobic (Peptostreptococcus micros, Peptostreptococcus magnus, Fusobacterium nucleatum, and Prevotella melaninogenica) bacteria associated with respiratory tract infections. Serum samples were obtained from 11 healthy male subjects following a single 400-mg oral dose of gatifloxacin and moxifloxacin. These samples were collected prior to and at 2, 6, 12, and 24 h after the dose of each drug. Gatifloxacin exhibited bactericidal activity for a median of 12 h against Streptococcus pneumoniae (MIC ‫؍‬ 0.5 g/ml), Peptostreptococcus micros (MIC ‫؍‬ 0.25 g/ml), and F. nucleatum (MIC ‫؍‬ 0.5 g/ml) and 24 h against H. influenzae (MIC ‫؍‬ 0.03 g/ml), Staphylococcus aureus (MIC ‫؍‬ 0.125 g/ml), Peptostreptococcus magnus (MIC ‫؍‬ 0.125 g/ml), and Prevotella melaninogenica (MIC ‫؍‬ 0.5 g/ml). Moxifloxacin exhibited bactericidal activity for a median of 24 h against Streptococcus pneumoniae (MIC ‫؍‬ 0.125 g/ml), H. influenzae (MIC ‫؍‬ 0.015 g/ml), Staphylococcus aureus (MIC ‫؍‬ 0.06 g/ml), F. nucleatum (MIC ‫؍‬ 0.5 g/ml), Prevotella melaninogenica (MIC ‫5.0؍‬ g/ml), Peptostreptococcus magnus (MIC ‫؍‬ 0.125 g/ml), and Peptostreptococcus micros (MIC ‫؍‬ 0.25 g/ml). The results from this pharmacodynamic study suggest that these fluoroquinolones would have prolonged killing activity against these organisms in vivo and may have clinical utility in the treatment of mixed aerobic-anaerobic respiratory tract infections.Gatifloxacin (Bristol-Myers Squibb) and moxifloxacin (Bayer) are new 8-methoxyfluoroquinolones with broad-spectrum antimicrobial activity which includes anaerobic bacteria (29). Both compounds have comparable in vitro activity against common aerobic and anaerobic respiratory pathogens (3). Moreover, they exhibit similar serum pharmacokinetics and penetration into respiratory tissues (9, 24). The ability of gatifloxacin and moxifloxacin to eradicate aerobic respiratory pathogens, such as Streptococcus pneumoniae and Haemophilus influenzae, has been well documented in pharmacodynamic models and clinical trials (9, 24). Their effectiveness in the treatment of anaerobic infections is unknown.In contrast to studies with aerobic bacteria, where concentration-dependent killing has been observed, concentrationindependent killing was discovered against Bacteroides thetaiotaomicron with various fluoroquinolones in an in vitro pharmacodynamic model (27). This model further discovered that resistant strains of Bacteroides fragilis emerged when the area under the concentration-time curve from 0 to 24 h (AUC 24 )-to-MIC ratio was less than 40 (26). In time-kill assays, maximal bactericidal activity against various anaerobes (B. fragilis, ...

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Serum Bactericidal Activity of Trovafloxacin Against Selected Anaerobic Pathogens

Cited by 3 publications

References 18 publications

Intra‐Abdominal Anaerobic Infections: Bacteriology and Therapeutic Potential of Newer Antimicrobial Carbapenem, Fluoroquinolone, and Desfluoroquinolone Therapeutic Agents

Intra‐Abdominal Anaerobic Infections: Bacteriology and Therapeutic Potential of Newer Antimicrobial Carbapenem, Fluoroquinolone, and Desfluoroquinolone Therapeutic Agents

Fluoroquinolones and Anaerobes

Bactericidal Activities of Methoxyfluoroquinolones Gatifloxacin and Moxifloxacin against Aerobic and Anaerobic Respiratory Pathogens in Serum

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